Pathologic staging of the mediastinal lymph nodes is

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1 Mediastinoscopy: Still the Gold Standard Joseph B. Shrager, MD Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, and Veterans Administration Palo Alto Healthcare System, Palo Alto, California Endobronchial ultrasound (EBUS-TBNA) is emerging as an alternative to mediastinoscopy for mediastinal lymph node evaluation in non-small cell lung cancer. It remains controversial whether EBUS-TBNA is as accurate as mediastinoscopy. Sensitivity appears similar to mediastinoscopy with enlarged nodes, but lower with normalsized nodes. The false negative rate appears higher than with mediastinoscopy, so nonmalignant EBUS results may be unreliable. Two flawed studies examining costs identify a very small cost benefit to EBUS, which we will question herein. There are scenarios in which EBUS is preferable to mediastinoscopy. However, for routine staging of the upper mediastinum in non-small cell lung cancer, the benefits of EBUS over mediastinoscopy remain unproven. (Ann Thorac Surg ) 2010 by The Society of Thoracic Surgeons Pathologic staging of the mediastinal lymph nodes is critically important in the triage of patients with nonsmall cell lung cancer (NSCLC) to various forms of therapy. Even with the advent of positron emission tomographycomputed tomography (PET/CT), radiographic staging of lymph nodes is notoriously inaccurate. Because some patients with mediastinal lymph node involvement should likely not be treated surgically (patients with N3 lymph node involvement and bulky or multistation N2 lymph node involvement), and other patients likely have their chances of cure substantially improved by induction chemotherapy or chemoradiation (lesser N2 lymph node involvement), it is in general not sufficient to rely upon these relatively inaccurate, noninvasive modes of mediastinal lymph nodes evaluation preoperatively. Mediastinoscopy, the traditional means of pathologic mediastinal lymph node evaluation prior to proceeding to definitive treatment of NSCLC, does require a fair amount of experience to perform effectively, efficiently, and safely. Most agree that it is relatively more difficult to teach than many other procedures, particularly prior to the introduction of video mediastinoscopy. There is no doubt that many surgeons would prefer to avoid the procedure altogether given the very rare but real occurrence of substantial bleeding complications. In part because of these concerns, endobronchial ultrasoundtransbronchial needle aspiration (EBUS-TBNA) has been introduced in recent years as an alternative mode of mediastinal lymph node sampling. The EBUS-TBNA allows needle-aspirate-sized samples to be taken from mediastinal lymph nodes as they are imaged in real time using an ultrasonic device positioned at the end of the bronchoscope. Presented at the 2 nd International Bi-Annual Minimally Invasive Thoracic Surgery Summit, Boston, MA, October 9 10, Address correspondence to Dr Shrager, Stanford University Hospital, Falk Research Bldg, 300 Pasteur Dr, Stanford, CA 94305; Shrager@stanford.edu. Many studies have been published, that, taken as a whole, suggest that EBUS-TBNA is at least comparable with mediastinoscopic evaluation of the mediastinal nodes. Advocates of the procedure, pointing to the best of the published results, have suggested that EBUS-TBNA should actually take over as the primary means of pathologic mediastinal lymph node evaluation, either alone or in combination with endoscopic ultrasound guided fine needle aspiration (EUS/FNA). After reviewing the data in this field, and also on the basis of extensive personal experience with mediastinoscopy and preliminary experience with EBUS/TNBA, I have come to the conclusion that although there are certainly specific situations where endobronchial ultrasound is useful, outside of these situations the technique provides little if any advantage over mediastinoscopy performed by an experienced operator. There are three main reported advantages of EBUS- TBNA over mediastinoscopy. These are that EBUS-TBNA is: (1) less invasive; (2) less expensive; and (3) equally accurate to mediastinoscopy. We will cover each of these purported advantages in sequence, and argue that in at least the latter two of these three areas, mediastinoscopy still provides greater benefits for our patients. The Claim That EBUS-TBA Is Less Invasive Than Mediastinoscopy It is fairly difficult for a procedure to be less invasive than an operation done through a 2-cm-long cervical incision on an outpatient basis. More specifically, advocates of EBUS-TBNA have argued that EBUS is less invasive first of all because it does not require general anesthesia (GA), and second of all because it has a lower complication rate. Dr Shrager has no conflicts of interest to disclose by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg MINIMALLY INVASIVE THORACIC SURGERY SUMMIT 2009 SHRAGER S2085 Beginning with the issue of GA, it is curious that this argument is made so often in favor of EBUS-TBNA when in fact, when one looks at all the published studies of EBUS-TBNA in the literature (see data below), less than 40% of them actually performed the procedure consistently using anything other than GA. So there is, in fact, very little evidence that the procedure can be reliably and reproducibly performed without GA. Complicated bronchoscopic procedures can be quite uncomfortable for patients and it is difficult to keep patients from coughing or otherwise moving about without GA. Certainly, a technique like EBUS-TNBA that requires multiple needle sticks in multiple areas of the airway (if the procedure is to be done effectively) is unlikely to be done well without GA. Thus, the argument that EBUS-TBNA does not require GA while mediastinoscopy does is not a valid one. On the issue of complication rates, EBUS-TBNA does appear to have a lower complication rate than mediastinoscopy, and when complications do occur they are less severe than those that occur after mediastinoscopy. There is no doubt that serious complications of EBUS- TBNA are extremely rare, and life-threatening complications after EBUS-TBNA are almost unheard of. On the other hand, while mediastinoscopy can rarely lead to serious complications, this is extraordinarily rare in experienced hands. In the largest published single institution series on mediastinoscopy of which I am aware [1], 4 surgical complications (0.19%) occurred in 2,137 consecutive patients undergoing mediastinoscopy. These included two episodes of bleeding; one esophageal injury and one pneumothorax. One of these surgical complications (0.04%) led to a death. These are very low major complication rates indeed. If one includes as a complication the problem of having a false negative lymph node sampling then the complication rate of EBUS-TBNA would be substantially higher than that of mediastinoscopy (see data below). In fact, a false negative lymph node sampling is far more likely to lead to death than is a complication of mediastinoscopy. A false negative lymph node sampling, for example, might lead to a pulmonary resection that has no chance of curing the patient in the case of unrecognized N3 disease, and it might lead to the absence of indicated induction therapy in the case of missed N2 disease. Unnecessary operation in N3 disease would subject a patient to at least a 1% risk of death from a futile operation, and the available evidence suggests that induction therapy may double the cure rate of a patient undergoing surgical resection for stage IIIA (N2) NSCLC. I will discuss later the data which suggest that one will have more false negative lymph node samplings with EBUS/FNA than with a mediastinoscopy. The Claim That EBUS-TBNA Is Less Expensive Than Mediastinoscopy The next topic that bears discussion is whether it is true that EBUS-TBNA is less expensive than mediastinoscopy. The argument that is frequently made is that mediastinoscopy uses operating time whereas EBUS does not, and that mediastinoscopy causes loss of work days that EBUS-TBNA may not require. These arguments, however, once again assume that the EBUS- TBNA is being done under local anesthesia, which appears not generally to be the case. Any procedure done under GA is going to require at least that the patient take the day of the procedure off from work. Endobronchial ultrasound, like mediastinoscopy, then will require that patients take the day of the procedure off from work. In the United States at least, mediastinoscopy is routinely done as an outpatient procedure. Postoperative pain is minimal and patients are certainly able to go back to work a day or two after the procedure. Issues of use of operating time and loss of work days therefore do not really work out substantially in favor of EBUS-TBNA. In addition, one has to take into account all of the hidden costs of endobronchial ultrasound. These include the EBUS bronchoscope itself, which costs at a minimum $30,000, and reusables with each case that are going to cost, at a minimum, $100 to $200. Two studies in the literature directly study the costs of EBUS-TBNA. Harewood and colleagues [2] estimated the cost of mediastinoscopy versus EBUS-TBNA on a per patient basis and came to the conclusion that the cost of mediastinoscopy is $20,157 and the cost of EBUS-TBNA is $19,828. This minor difference comes to a total of $329, or 1.6% of the total estimated cost of the mediastinscopy. However, my reading of this paper suggests major errors in assumptions that, if accounted for, would actually render mediastinoscopy less costly than EBUS-TBNA. First, the authors assume that mediastinoscopy was done as a separate procedure from the thoracotomy. It is well established in a study by Kim and colleagues [3] that staging mediastinoscopy at a separate anesthetic from pulmonary resection is substantially more expensive than performing simultaneous mediastinoscopy and pulmonary resection. This retrospective study showed that the operating room time was 1.2 hours less when the procedures were done simultaneously, and the overall costs were 25% lower. If Harewood and colleagues had assumed that mediastinoscopy was done simultaneous to thoracotomy, which is clearly feasible and in many centers the standard practice, then the cost of mediastinoscopy would fall to about $15,000, which is 25% less than the cost of EBUS-TBNA. An additional error in the assumptions made in the study by Harewood and colleagues is that 50% of the mediastinoscopy patients will be admitted overnight. Obviously, this becomes an irrelevant issue if the mediastinoscopies are done at the same time as the pulmonary resection, but in the United States the mediastinoscopy, if done separately, is essentially always performed as an outpatient procedure. Therefore, if one is to analyze mediastinoscopy being done as a separate procedure, cost should not include an overnight stay for more than 1% or 2% of patients. Overall, then, the study by Harewood and colleagues actually provides evidence that mediastinoscopy is more cost effective than EBUS-TBNA. The only other study evaluating the cost of EBUS- TBNA compared with mediastinoscopy is in an extended

3 S2086 MINIMALLY INVASIVE THORACIC SURGERY SUMMIT 2009 SHRAGER Ann Thorac Surg letter to the editor by Callister and colleagues published in Thorax [4]. These authors, again making a number of assumptions that one could take issue with, found that EBUS-TBNA would save their local British National Health System region 32,000 per year in the evaluation of mediastinal lymph nodes in NSCLC patients. That is 32,000 per year in total savings that they calculated for their entire region, not 32,000 per patient. In other words, the savings were quite low on a per patient basis. Additionally, it appears that one of the assumptions made in this study are that PET/CT would not be performed if EBUS-TBNA were performed. Under this assumption, the use of EBUS-TBNA is offset by savings on PET/CT scans. However, in the United States, PET/CT is essentially always performed in patients with known or suspected NSCLC, and this is done in addition to any pathologic mediastinal evaluation. Further, as I will review below, the accuracy of EBUS is highly dependent on PET/CT and CT findings. Therefore, if one were to eliminate PET/CT from the diagnostic protocol, EBUS would be far less accurate. Finally, this study, similar to the Harewood and colleagues study [2], assumed an overnight stay for all mediastinoscopies. A final point, and an important one to mention when discussing the cost of EBUS-TBNA versus mediastinoscopy, is that the performance of EBUS-TBNA quite often does not eliminate the need for a mediastinoscopy. That is, the fact that EBUS-TBNA is performed does not mean that a mediastinoscopy will not also need to be performed. On the other hand, if a mediastinoscopy is performed, it is clear that EBUS- TBNA will not need to be performed. The greater false negative rate of EBUS-TBNA, which will be discussed below, in my view requires that mediastinoscopy be performed to confirm the negative results of the EBUS- TBNA. As a result, it is not appropriate to compare the costs of, for example, 10 EBUS-TBNAs to 10 mediastinoscopies. It would probably be more appropriate to compare the cost of 10 EBUS-TBNAs plus 1 to 2 mediastinoscopies performed for negative EBUS-TBNAs, to the cost of 10 mediastinoscopies. The Claim That EBUS-TBNA Has Equal Accuracy to Mediastinoscopy The last topic, and perhaps the most important area to cover, is the claim that EBUS-TBNA is equally accurate in staging the mediastinal lymph nodes as is mediastinoscopy. Before delving more deeply into this issue, it should be said that there has never been a needle-based biopsy technique that had equal reliability to a biopsy technique that is able to obtain a larger piece of tissue. In fact, it is safe to say that it is not possible that a needle-based assay could be equally reliable to a sampling technique that allows larger pieces of tissue to be obtained at biopsy. The best example of this phenomenon within thoracic surgery is CT-guided transthoracic needle biopsy of lung lesions. There will always be a certain incidence of false negative results from any needle-based biopsy technique, and over the years this has been clearly demonstrated for transthoracic needle biopsy of lung lesions. Additionally, it has been amply demonstrated that core biopsies which provide a larger piece of tissue are more reliable than fine needle aspirations. It simply has to be true that needle aspiration of lymph nodes will be less accurate than the larger biopsies that one is able to obtain with mediastinoscopy. There is almost certainly significant publication bias in the available literature on the sensitivity and specificity for EBUS-TBNA of mediastinal lymph nodes. Certainly, those with results that are far inferior to those published by other groups are not going to publish those results. Even with this phenomenon, however, one can point to two, separate, published meta-analyses that on careful analysis support the contention that EBUS-TBNA is not as accurate as mediastinoscopy. The first of these meta-analyses was published by Adams and colleagues [5]. This publication reviewed 10 studies which met the criteria for inclusion covering a total of 692 patients who underwent EBUS-TBNA. Overall sensitivity was 88%, but there were 2 studies reviewed with sensitivities below 70%. It is also important to point out that GA was used in 6 out of 10 of these studies, again rendering less convincing the argument that EBUS- TBNA can be performed under local anesthesia with high accuracy. The second meta-analysis was published by Gu and colleagues [6]. This meta-analysis included 11 studies and 1,299 patients. Only 3 studies overlap between the 2 meta-analyses. Here, the overall sensitivity was 93%. However, the authors looked separately at studies in which the patients were not selected by preoperative CT or PET/CT that suggested lymph node involvement. In these unselected patients, sensitivity was only 76%, which is well below the sensitivity of mediastinoscopy in similar, unselected patient cohorts. And again, most of these studies used GA rather than local anesthesia and sedation. Frank Detterbeck, as leader of a group that created the American College of Chest Physician (ACCP) guideline for evaluation of mediastinal lymph nodes, performed a separate systematic review of the literature on mediastinoscopy and EBUS-TBNA [7]. The analysis of this systematic review, and the resulting ACCP guideline, honed in very accurately on the weaknesses of EBUS-TBNA and the vagaries of the literature in this area. This group reviewed 8 studies of mediastinoscopic staging with a total of 918 patients, and 17 studies of EBUS-TBNA staging with a total of 1,239 patients. The mediastinoscopy studies showed sensitivity of 80% (90% with video mediastinoscopy), and a false negative rate of 10%. The EBUS-TBNA studies show a sensitivity of 90%, but a very high false negative rate of 24%. On further analysis of these studies, the ACCP guideline writing group described four separate radiologic groups of mediastinal lymph nodes which are encountered in caring for lung cancer patients, and which are contained in varying degrees in each of the EBUS and mediastinoscopy studies evaluated. These radiologic groups included the following: (1) patients with obvious mediastinal infiltration; (2) patients with discreet medi-

4 Ann Thorac Surg MINIMALLY INVASIVE THORACIC SURGERY SUMMIT 2009 SHRAGER S2087 astinal lymph node enlargement; (3) patients with enlargement of one lymph node or no lymph node enlargement with a central primary tumor; (4) patients with no lymph node enlargement and a peripheral T1 or T2 tumor. The writing group also noted that, within the studies evaluated, there was a wide mix of indications for the mediastinoscopy or EBUS-TBNA. For example, in some cases the primary issue was simple confirmation of a diagnosis, in some the issue was confirmation of nodal involvement that was highly suspected on the basis of imaging studies, whereas in other cases the indication was confirmation of a lack of nodal involvement. The EBUS-TBNA studies tended to include patients with discreet lymph node enlargement where the TBNA was done more for confirmation of suspected mediastinal lymph node disease rather than ruling out lymph node disease that was felt unlikely to be present based on imaging. This would clearly tend to inflate the sensitivity of the EBUS-TBNA and reduce the false negative rate. Even with this difference in the patients studied, it is extremely concerning that the false negative rate with EBUS-TBNA would still be more than double that of mediastinoscopy. Similarly, it is very likely the slightly higher sensitivity rate found on average in the EBUS- TBNA studies and the mediastinoscopy studies is due more to types of patients enrolled rather than the intrinsic properties of the sampling technique. On the basis of this very careful analysis of the published data, the ACCP committee came to the conclusions that can be summarized as follows. For patients with discreet mediastinal lymph node enlargement, either mediastinoscopy or EBUS are reasonable. Even in this group, however, they recommend that a nonmalignant result from EBUS-TBNA should be confirmed by a mediastinoscopy. For patients without mediastinal lymph node enlargement, the recommendation is that mediastinoscopy is favored because of its likely greater sensitivity for lesser degrees of lymph node involvement and its lower false negative rate, but that EBUS-TBNA may be reasonable as long as it is followed by a mediastinoscopy if a nonmalignant result is obtained by EBUS-TBNA. If, however, one takes the thought process that led to these recommendations to their logical conclusions, one cannot really recommend EBUS strongly over mediastinoscopy in any situation. The reason for this is that, when a patient has clinical N2 disease, an important part of the value of mediastinoscopy is to rule out N3 disease which would render a patient unresectable. As the false negative rate of endobronchial ultrasound with nonenlarged lymph nodes is unacceptably high, although you might be able to accurately determine N2 disease with EBUS-TBNA alone in patients who have radiographically enlarged or PET positive ipsilateral mediastinal nodes, you may very well miss the presence of microscopic, contralateral N3 disease. Subtleties such as this are difficult to capture in clinical studies, but only by considering them can we decide on what is the most appropriate way to stage mediastinal lymph nodes in a particular patient. Circling back again to cost issues; if one follows the ACCP guidelines, it appears that costs are likely to be increased. Where patients who have a mediastinoscopy done primarily will need to have only one procedure, if we now do EBUS first, but then do a mediastinoscopy additionally if the EBUS has a negative result, we have now replaced one procedure with two procedures. If this has to be done in 10 to 20% of the patients, this is a substantial increase in both cost and inconvenience to our patients. Finally, it is important to point out that even in the most recently published studies of EBUS-TBNA, from some of the most experienced centers, the sensitivity and in particular the negative predictor value do not look to be substantially improving. For example, Ømark Petersen and colleagues [8] reported a sensitivity of only 85% in their 2009 publication. Ernst and colleagues, in their most recent publication [9] reported a sensitivity of 87% and a negative predictor value of only 78%. Although in that latter study, this sensitivity and negative predictor value was better than mediastinoscopy (to which EBUS/TBNA was compared head to head), it appears that for some reason the surgeons who performed mediastinoscopy in this study were not comfortable biopsying the subcarinal lymph nodes. This appears to have significantly and negatively influenced the mediastinoscopy results. Which Technique Reaches Additional Lymph Nodes? One sometimes hears the argument being made in favor of EBUS-TBNA that it allows us to reach lymph nodes not previously accessible. It is true that EBUS-TBNA allows N1 lymph nodes to be sampled, whereas this is not possible by mediastinoscopy without a very aggressive dissection with which most surgeons are not comfortable. However, whether or not a patient has involved N1 lymph nodes currently has no therapeutic implications. Patients with N1 disease are not given neoadjuvant chemotherapy as there has not been shown to be any benefit to this, and patients with N1 lymph node involvement are certainly not denied resection if they have an acceptable risk profile for surgery. It is possible that in the future the ability to identify N1 lymph node involvement preoperatively will have therapeutic value (for example, if thoracoscopic wedge resection or stereotactic body radiotherapy become more widely used treatment modalities), but at the current time this is not the case. It is in fact EUS/FNA and not EBUS-TBNA that allows one to assess additional mediastinal nodal groups beyond what is reachable by mediastinoscopy. The EUS- FNA allows one to reach level 8 lymph nodes, level 9 lymph nodes, and lymph nodes in the aortic pulmonary window. In certain clinical instances evaluation of these lymph nodes may be valuable, so if there is any endoscopic mediastinal staging procedure that adds value to mediastinoscopy it is the EUS/FNA, not the EBUS-TBNA.

5 S2088 MINIMALLY INVASIVE THORACIC SURGERY SUMMIT 2009 SHRAGER Ann Thorac Surg Specific Advantages of EBUS-TBNA Although from data that we have reviewed above it does not appear that EBUS-TBNA should replace mediastinoscopy for the routine pathologic staging of mediastinal lymph nodes, there are clearly specific situations in which EBUS-TBNA does have an advantage over mediastinoscopy. It is therefore advantageous to have EBUS- TBNA in one s armamentarium. The first of these situations was alluded to above, and that is the occasional case where it is meaningful to know whether N1 lymph nodes contain malignant cells or not. This may occur, for example, in a patient who one feels is a candidate for wedge resection or stereotactic body radiation but is not a candidate for lobectomy. Also, sampling clinically involved N1 lymph nodes may rarely be the easiest way to establish a tissue diagnosis in some patients; for example, a patient with severe emphysema and a peripheral lung nodule who is not a surgical candidate. This patient may be at high risk for pneumothorax from transthoracic needle biopsy, but sampling of the mediastinal lymph nodes by EBUS-TBNA may be fairly simple and can be done without that risk. I myself had a patient who appeared to have a right hilar recurrence after a pneumonectomy with complete mediastinal lymphadenectomy performed several years previously. The EBUS-TBNA was really the only way to access this area safely for confirmation of recurrence. The other situation in which EBUS may have advantages depends upon one s approach to patients with resectable N2 disease. If one believes, as this author does, that patients with single station, non-bulky N2 disease should be operated on after induction therapy regardless of whether their nodes have been rendered N0, then EBUS does not really have clear value. If one believes in this approach, then it is ideal, in my opinion, to begin with mediastinoscopy initially to establish the presence of N2 disease and the absence of N3 disease. If one believes in operating as long as there is no progression during the induction therapy, then there is no need to pathologically reevaluate the lymph nodes after the induction therapy, and therefore there is no concern about the difficulties of re-mediastinoscopy. The author s personal belief, which is supported by at least one report in literature, is that repeat mediastinoscopy is something to be avoided. A study by De Waele and colleagues [10] shows that re-mediastinoscopy carries 1% mortality and 3 to 4% risk of major morbidity including hemorrhage and inadvertent lung biopsy. In addition, the sensitivity of repeat of every mediastinoscopy is only 71% in this study. There are those, however, who believe that one should operate on N2 disease only if it has been sterilized by induction therapy. If one takes this approach, then it becomes important to restage the mediastinal lymph nodes pathologically after induction therapy. Because, as I said, re-mediastinoscopy is not an optimal approach, it would be best in this circumstance to obtain the initial pathologic confirmation of N2 disease by EBUS-TBNA. One is then able to do the mediastinoscopy after the induction therapy in a relatively clean field and without the difficulties of repeat mediastinoscopy. One other point does need to be made which is an appropriate argument in favor of the use of EBUS-TBNA in certain situations. Clinical studies consistently show that patients with nonbulky and non-multistation N2 lymph node involvement have quite acceptable cure rates after primary surgical resection. In fact, there has never been a study comparing induction therapy to postoperative chemotherapy for patients with stage 3A (N2) disease. The only studies that showed a benefit of preoperative chemotherapy for patients with stage 3A (N2) disease included many patients who had more than what we would today consider microscopically involved N2 disease. All of these data suggest that it may not be particularly important to identify patients with microscopic N2 disease preoperatively. If this is in fact the case, and it is not clear whether it will actually ever be proven or disproven, then the high false negative rates of EBUS- TBNA in the setting of clinically noninvolved lymph nodes may not be an important issue. Conclusions In summary, the benefits of EBUS-TBNA are difficult to clearly see other than in occasional, unusual clinical situations. If there are benefits to EBUS-TBNA over mediastinoscopy, they occur at the margins. Endobronchial ultrasound does prevent the very rare, severe complication of mediastinoscopy, but other than this, it is not in fact substantially less invasive than mediastinoscopy, particularly when it is performed under GA. The studies that evaluate costs of EBUS-TBNA versus mediastinoscopy do suggest to this reader that mediastinoscopy, if performed at the same sitting as lung resection, is actually less expensive than endobronchial ultrasound. This approach is also certainly more convenient for patients than having a separate visit with one physician for EBUS-TBNA prior to a visit with another physician for surgical resection. Lastly and probably most importantly, endobronchial ultrasound does not appear by my review of the literature to be as accurate as mediastinoscopy. It clearly has a higher false negative rate than mediastinoscopy, and in particular it has an unacceptably high false negative rate in patients with nonenlarged and (or) non-fluorodeoxyglucose-avid lymph nodes. In the opinion of this writer, what EBUS-TBNA achieves primarily, other than unusual cases in which it is a real aid, is to allow aggressive pulmonologists to begin to take a more central role in the staging and triage of lung cancer patients. It is incumbent upon us as thoracic surgeons, who are likely those who have the greatest grasp on the biology NSCLC, to present to our colleagues our concerns about the operating characteristics of EBUS-TBNA in the setting of lymph nodes that are not clinically involved. The disinformation disseminated by the overly sanguine presentations about EBUS-TBNA that one generally hears from its advocates must be balanced by careful consideration of the true pros and cons of the technique.

6 Ann Thorac Surg MINIMALLY INVASIVE THORACIC SURGERY SUMMIT 2009 SHRAGER S2089 In closing, it is important to point out that it is probably unlikely that one is going to do any significant harm to a patient by using EBUS-TBNA to stage mediastinal lymph nodes, as long as one does it in a very careful and data-driven manner. That is, as long as one believes it is important to know preoperatively whether patients have N2 lymph node involvement or not, EBUS-TBNA should be applied only to patients who have clinically involved nodes (either enlarged or fluorodeoxyglucose-avid); three aspirates at a minimum should be done of every lymph node, with 10 passes per aspirate, N3 lymph nodes that can be identified should be sampled as well, and any and all negative results should be followed up with a mediastinoscopy. Doing this requires a great deal of patience, and I think it is very unlikely that it can be done without GA. Only an approach with this kind of attention to detail will provide results that approach those of a mediastinoscopy performed by an experienced surgeon. The author would like to thank Donna Minagawa for technical assistance with the manuscript preparation. References 1. Hammoud ZT, Anderson RC, Meyers BF, et al. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg 1999;118: Harewood GC, Pascual J, Raimondo M, et al. Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer. Lung Cancer 2010;67: Kim K, Rice TW, Murthy SC, et al. Combined bronchoscopy, mediastinoscopy, and thoracotomy for lung cancer: who benefits? J Thorac Cardiovasc Surg 2004;127: Callister ME, Gill A, Allott W, Plant PK. Endobronchial ultrasound guided transbronchial needle aspiration of mediastinal lymph nodes for lung cancer staging: a projected cost analysis. Thorax 2008;63: Adams K, Shah PL, Edmonds L, Lim E. Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis. Thorax 2009; 64: Gu P, Zhao YZ, Jiang LY, Zhang W, Xin Y, Han BH. Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis. Eur J Cancer 2009;45: Detterbeck FC, Jantz MA, Wallace M, Vansteenkiste J, Silvestri GA; American College of Chest Physicians. Invasive mediastinal staging of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(3 suppl):202s 20S. 8. Ømark Petersen H, Eckardt J, Hakami A, Olsen KE, Jørgensen OD. The value of mediastinal staging with endobronchial ultrasound-guided transbronchial needle aspiration in patients with lung cancer. Eur J Cardiothorac Surg 2009;36: Ernst A, Anantham D, Eberhardt R, Krasnik M, Herth FJ. Diagnosis of mediastinal adenopathy-real-time endobronchial ultrasound guided needle aspiration versus mediastinoscopy. J Thorac Oncol 2008;3: De Waele M, Serra-Mitjans M, Hendriks J, et al. Accuracy and survival of repeat mediastinoscopy after induction therapy for non-small cell lung cancer in a combined series of 104 patients. Eur J Cardiothorac Surg 2008;33:824 8.